Abstract

We demonstrate in vivo measurements in human retinal vessels of an experimental parameter, the slope of the low coherence interferometry (LCI) depth reflectivity profile, which strongly correlates with the real value of blood hematocrit. A novel instrument that combines two technologies, spectral domain low coherence interferometry (SDLCI) and retinal tracking, has been developed and used for these measurements. Retinal tracking allows a light beam to be stabilized on retinal vessels, while SDLCI is used for obtaining depth-reflectivity profiles within the investigated vessel. SDLCI backscatter extinction rates are obtained from the initial slope of the A-scan profile within the vessel lumen. The differences in the slopes of the depth reflectivity profiles for different subjects are interpreted as the difference in the scattering coefficient, which is correlated with the number density of red blood cells (RBC) in blood. With proper calibration, it is possible to determine hematocrit in retinal vessels. Ex vivo measurements at various RBC concentrations were performed to calibrate the instrument. Preliminary measurements on several healthy volunteers show estimated hematocrit values within the normal clinical range.

© 2006 Optical Society of America

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    [CrossRef]
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    [CrossRef]

2005 (6)

W. Secomsky, A. Nowicki, F. Guidi, P. Tortoli, and P.A. Lewin, "Non-invasive measurement of blood hematocrit in artery," Bulletin of the Polish Academy of Sciences,  53 (3), 245-50 (2005).

H. Liang, M. G. Cid, R. G. Cucu, G. M. Dobre, A. G. Podoleanu, J. Pedro, and D. Saunders, "En-face optical coherence tomography - a novel application of non-invasive imaging to art conservation," Opt. Express 13,6133-6144 (2005).
[CrossRef] [PubMed]

J. Zhang and Z. Chen, "In vivo blood flow imaging by a swept laser source based Fourier domain optical Doppler tomography," Opt. Express 13,7449-7457 (2005).
[CrossRef] [PubMed]

D. X. Hammer, R. D. Ferguson, N. V. Iftimia, T. Ustun, G. Wollstein, H. Ishikawa, M. L. Gabriele, W. D. Dilworth, L. Kagemann, and J. S. Schuman, "Advanced scanning methods with tracking optical coherence tomography," Opt. Express 13,7937-7947 (2005).
[CrossRef] [PubMed]

M Yu Kirillin, A.V. Priezzhev, V V Tuchin, R K Wang, and R Myllylä, "Effect of red blood cell aggregation and sedimentation on optical coherence tomography signals from blood samples," J. Phys. D: Appl. Phys. 382582-2589 (2005).
[CrossRef]

D. J. Faber, E.G. Mick, M.C.G. Aalders, T.G. van Leeuwen, "Toward assessment of blood oxygen saturation by spectroscopic optical coherence tomography," Optt. Lett. 30(9), 1015-17 (2005).
[CrossRef]

2004 (6)

M. Wojtkowski, V. J. Srinivasan, T. H. Ko, J. G. Fujimoto, A. Kowalczyk, and J. S. Duker, "Ultrahigh-resolution, high-speed, Fourier domain optical coherence tomography and methods for dispersion compensation," Opt. Express 12, 2404-2422 (2004).
[CrossRef] [PubMed]

L. Thrahe, M.H. Frosz, T.M. Jørgensen, A. Tycho, H.T. Yura, P.E. Andersen, " Extraction of optical scattering parameters and attenuation compensation in optical coherence tomography images of multilayered tissue structures," Opt. Lett. 29(14), 1641-43 (2004).
[CrossRef]

C. Xu, D. L. Marks, M. N. Do, and S. A. Boppart, "Separation of absorption and scattering profiles in spectroscopic optical coherence tomography using a least-squares algorithm," Opt. Express 12,4790-4803 (2004).
[CrossRef] [PubMed]

B. Hermann, K. Bizheva, A. Unterhuber, B. Povazay, H. Sattmann, L. Schmetterer, A. F. Fercher and W. Drexler, "Precision of extracting absorption profiles from weakly scattering media with spectroscopic time-domain optical coherence tomography," Opt. Express 12, 1677-1688 (2004).
[CrossRef] [PubMed]

B.R. White, M.C. Pierce, N. Nassif,  et al., "In vivo dynamic human retinal blood flow imaging using ultra-highspeed spectral domain optical Doppler tomography," Opt. Express 11, 3490-3497 (2004).
[CrossRef]

N.A. Nassif, B. Cense, B.H. Park,  et al., "In vivo high-resolution video-rate spectral-domain optical coherence tomography of the human retina and optic nerve," Opt. Express 12, 367-376 (2004).
[CrossRef] [PubMed]

2003 (5)

2002 (1)

1999 (1)

A. Roggan, M. Friebel, K. Dörschel, A. Hahn, and G. Müller, "Optical Properties of Circulating Human Blood in the Wavelength Range 400-2500 nm," J. Biomed. Opt. 4, 36-46 (1999).
[CrossRef]

1998 (2)

G. Hausler and M. W. Lindner, "Coherence radar and spectral radar - new tools for dermatological diagnosis," J. Biomed. Opt. 3, 21-31 (1998).
[CrossRef]

C. Johner, P. Chamney, D. Schneditz, and M. Krämer, "Evaluation of an ultrasonic blood volume monitor," Nephrol. Dial. Transplant. 13, 2098-2103 (1998).
[CrossRef] [PubMed]

1992 (1)

J.M. Schmitt, Z Guan-Xiong, and J. Miller, "Measurement of blood hematocrit by dual-wavelength near-IR photoplethsymography, " Proc. SPIE 1441, 150-161 (1992).
[CrossRef]

1988 (1)

1987 (1)

1970 (1)

Aalders, M.C.G.

D. J. Faber, E.G. Mick, M.C.G. Aalders, T.G. van Leeuwen, "Toward assessment of blood oxygen saturation by spectroscopic optical coherence tomography," Optt. Lett. 30(9), 1015-17 (2005).
[CrossRef]

Andersen, P.E.

Bizheva, K.

Boppart, S. A.

Bouma, B. E.

Cense, B.

Chamney, P.

C. Johner, P. Chamney, D. Schneditz, and M. Krämer, "Evaluation of an ultrasonic blood volume monitor," Nephrol. Dial. Transplant. 13, 2098-2103 (1998).
[CrossRef] [PubMed]

Chen, Z.

Cid, M. G.

Cornsweet, T. N.

Crane, H. D.

Cucu, R. G.

de Boer, J. F.

de Boer, J.F.

Dilworth, W. D.

Do, M. N.

Dobre, G. M.

Dörschel, K.

A. Roggan, M. Friebel, K. Dörschel, A. Hahn, and G. Müller, "Optical Properties of Circulating Human Blood in the Wavelength Range 400-2500 nm," J. Biomed. Opt. 4, 36-46 (1999).
[CrossRef]

Drexler, W.

Duker, J. S.

Elsner, A. E.

Faber, D. J.

D. J. Faber, E.G. Mick, M.C.G. Aalders, T.G. van Leeuwen, "Toward assessment of blood oxygen saturation by spectroscopic optical coherence tomography," Optt. Lett. 30(9), 1015-17 (2005).
[CrossRef]

D. J. Faber, E.G. mick, M.C.G. Aalders, T.G. van Leeuwen, "Light absorption of (oxy-)hemoglobin assessed by spectroscopic optical coherence tomography," Opt. Lett 28(16), 1436-38 (2003).
[CrossRef] [PubMed]

Fercher, A. F.

Ferguson, R. D.

Friebel, M.

A. Roggan, M. Friebel, K. Dörschel, A. Hahn, and G. Müller, "Optical Properties of Circulating Human Blood in the Wavelength Range 400-2500 nm," J. Biomed. Opt. 4, 36-46 (1999).
[CrossRef]

Frosz, M.H.

Fujimoto, J. G.

Gabriele, M. L.

Guan-Xiong, Z

J.M. Schmitt, Z Guan-Xiong, and J. Miller, "Measurement of blood hematocrit by dual-wavelength near-IR photoplethsymography, " Proc. SPIE 1441, 150-161 (1992).
[CrossRef]

Guidi, F.

W. Secomsky, A. Nowicki, F. Guidi, P. Tortoli, and P.A. Lewin, "Non-invasive measurement of blood hematocrit in artery," Bulletin of the Polish Academy of Sciences,  53 (3), 245-50 (2005).

Hahn, A.

A. Roggan, M. Friebel, K. Dörschel, A. Hahn, and G. Müller, "Optical Properties of Circulating Human Blood in the Wavelength Range 400-2500 nm," J. Biomed. Opt. 4, 36-46 (1999).
[CrossRef]

Hammer, D. X.

Hausler, G.

G. Hausler and M. W. Lindner, "Coherence radar and spectral radar - new tools for dermatological diagnosis," J. Biomed. Opt. 3, 21-31 (1998).
[CrossRef]

Hermann, B.

Hitzenberger, C. K.

R. Leitgeb, C. K. Hitzenberger, and A. F. Fercher, "Performance of Fourier domain vs. time domain optical coherence tomography," Opt. Express 11, 889-894 (2003). [REMOVED HYPERLINK FIELD]
[CrossRef] [PubMed]

A. F. Fercher, W. Drexler, C. K. Hitzenberger and T. Lasser, "Optical coherence tomography- principles and application," Rep. Prog. Phys. 66. 239-303 (2003).
[CrossRef]

Hughes, G. W.

Iftimia, N.

Iftimia, N. V.

Ishikawa, H.

Johner, C.

C. Johner, P. Chamney, D. Schneditz, and M. Krämer, "Evaluation of an ultrasonic blood volume monitor," Nephrol. Dial. Transplant. 13, 2098-2103 (1998).
[CrossRef] [PubMed]

Jørgensen, T.M.

Kagemann, L.

Ko, T. H.

Kowalczyk, A.

Krämer, M.

C. Johner, P. Chamney, D. Schneditz, and M. Krämer, "Evaluation of an ultrasonic blood volume monitor," Nephrol. Dial. Transplant. 13, 2098-2103 (1998).
[CrossRef] [PubMed]

Lasser, T.

A. F. Fercher, W. Drexler, C. K. Hitzenberger and T. Lasser, "Optical coherence tomography- principles and application," Rep. Prog. Phys. 66. 239-303 (2003).
[CrossRef]

Leitgeb, R.

Lewin, P.A.

W. Secomsky, A. Nowicki, F. Guidi, P. Tortoli, and P.A. Lewin, "Non-invasive measurement of blood hematocrit in artery," Bulletin of the Polish Academy of Sciences,  53 (3), 245-50 (2005).

Liang, H.

Lindner, M. W.

G. Hausler and M. W. Lindner, "Coherence radar and spectral radar - new tools for dermatological diagnosis," J. Biomed. Opt. 3, 21-31 (1998).
[CrossRef]

Magill, J. C.

Marks, D. L.

Mick, E.G.

D. J. Faber, E.G. Mick, M.C.G. Aalders, T.G. van Leeuwen, "Toward assessment of blood oxygen saturation by spectroscopic optical coherence tomography," Optt. Lett. 30(9), 1015-17 (2005).
[CrossRef]

Miller, J.

J.M. Schmitt, Z Guan-Xiong, and J. Miller, "Measurement of blood hematocrit by dual-wavelength near-IR photoplethsymography, " Proc. SPIE 1441, 150-161 (1992).
[CrossRef]

Müller, G.

A. Roggan, M. Friebel, K. Dörschel, A. Hahn, and G. Müller, "Optical Properties of Circulating Human Blood in the Wavelength Range 400-2500 nm," J. Biomed. Opt. 4, 36-46 (1999).
[CrossRef]

Myllylä, R

M Yu Kirillin, A.V. Priezzhev, V V Tuchin, R K Wang, and R Myllylä, "Effect of red blood cell aggregation and sedimentation on optical coherence tomography signals from blood samples," J. Phys. D: Appl. Phys. 382582-2589 (2005).
[CrossRef]

Nassif, N.

Nassif, N.A.

Nowicki, A.

W. Secomsky, A. Nowicki, F. Guidi, P. Tortoli, and P.A. Lewin, "Non-invasive measurement of blood hematocrit in artery," Bulletin of the Polish Academy of Sciences,  53 (3), 245-50 (2005).

Park, B.H.

Pedro, J.

Pierce, M.C.

Podoleanu, A. G.

Povazay, B.

Priezzhev, A.V.

M Yu Kirillin, A.V. Priezzhev, V V Tuchin, R K Wang, and R Myllylä, "Effect of red blood cell aggregation and sedimentation on optical coherence tomography signals from blood samples," J. Phys. D: Appl. Phys. 382582-2589 (2005).
[CrossRef]

Roggan, A.

A. Roggan, M. Friebel, K. Dörschel, A. Hahn, and G. Müller, "Optical Properties of Circulating Human Blood in the Wavelength Range 400-2500 nm," J. Biomed. Opt. 4, 36-46 (1999).
[CrossRef]

Sattmann, H.

Saunders, D.

Schmetterer, L.

Schmitt, J.M.

J.M. Schmitt, Z Guan-Xiong, and J. Miller, "Measurement of blood hematocrit by dual-wavelength near-IR photoplethsymography, " Proc. SPIE 1441, 150-161 (1992).
[CrossRef]

Schneditz, D.

C. Johner, P. Chamney, D. Schneditz, and M. Krämer, "Evaluation of an ultrasonic blood volume monitor," Nephrol. Dial. Transplant. 13, 2098-2103 (1998).
[CrossRef] [PubMed]

Schuman, J. S.

Secomsky, W.

W. Secomsky, A. Nowicki, F. Guidi, P. Tortoli, and P.A. Lewin, "Non-invasive measurement of blood hematocrit in artery," Bulletin of the Polish Academy of Sciences,  53 (3), 245-50 (2005).

Shepherd, A.P.

Srinivasan, V. J.

Steinke, J.M.

Tearney, G. J.

Thrahe, L.

Tortoli, P.

W. Secomsky, A. Nowicki, F. Guidi, P. Tortoli, and P.A. Lewin, "Non-invasive measurement of blood hematocrit in artery," Bulletin of the Polish Academy of Sciences,  53 (3), 245-50 (2005).

Tuchin, V V

M Yu Kirillin, A.V. Priezzhev, V V Tuchin, R K Wang, and R Myllylä, "Effect of red blood cell aggregation and sedimentation on optical coherence tomography signals from blood samples," J. Phys. D: Appl. Phys. 382582-2589 (2005).
[CrossRef]

Tycho, A.

Unterhuber, A.

Ustun, T.

van Leeuwen, T.G.

D. J. Faber, E.G. Mick, M.C.G. Aalders, T.G. van Leeuwen, "Toward assessment of blood oxygen saturation by spectroscopic optical coherence tomography," Optt. Lett. 30(9), 1015-17 (2005).
[CrossRef]

Wang, R K

M Yu Kirillin, A.V. Priezzhev, V V Tuchin, R K Wang, and R Myllylä, "Effect of red blood cell aggregation and sedimentation on optical coherence tomography signals from blood samples," J. Phys. D: Appl. Phys. 382582-2589 (2005).
[CrossRef]

Webb, R. H.

White, B.R.

White, M. A.

Wojtkowski, M.

Wollstein, G.

Wornson, D. P.

Xu, C.

Yu Kirillin, M

M Yu Kirillin, A.V. Priezzhev, V V Tuchin, R K Wang, and R Myllylä, "Effect of red blood cell aggregation and sedimentation on optical coherence tomography signals from blood samples," J. Phys. D: Appl. Phys. 382582-2589 (2005).
[CrossRef]

Yun, S. H.

Yura, H.T.

Zhang, J.

Appl. Opt. (1)

Bulletin of the Polish Academy of Sciences (1)

W. Secomsky, A. Nowicki, F. Guidi, P. Tortoli, and P.A. Lewin, "Non-invasive measurement of blood hematocrit in artery," Bulletin of the Polish Academy of Sciences,  53 (3), 245-50 (2005).

J. Biomed. Opt. (2)

G. Hausler and M. W. Lindner, "Coherence radar and spectral radar - new tools for dermatological diagnosis," J. Biomed. Opt. 3, 21-31 (1998).
[CrossRef]

A. Roggan, M. Friebel, K. Dörschel, A. Hahn, and G. Müller, "Optical Properties of Circulating Human Blood in the Wavelength Range 400-2500 nm," J. Biomed. Opt. 4, 36-46 (1999).
[CrossRef]

J. Opt. Soc. Am. (1)

J. Opt. Soc. Am. A (1)

J. Phys. D: Appl. Phys. (1)

M Yu Kirillin, A.V. Priezzhev, V V Tuchin, R K Wang, and R Myllylä, "Effect of red blood cell aggregation and sedimentation on optical coherence tomography signals from blood samples," J. Phys. D: Appl. Phys. 382582-2589 (2005).
[CrossRef]

Nephrol. Dial. Transplant. (1)

C. Johner, P. Chamney, D. Schneditz, and M. Krämer, "Evaluation of an ultrasonic blood volume monitor," Nephrol. Dial. Transplant. 13, 2098-2103 (1998).
[CrossRef] [PubMed]

Opt. Express (11)

D. X. Hammer, R. D. Ferguson, J. C. Magill, M. A. White, A. E. Elsner, and R. H. Webb, "Image stabilization for scanning laser ophthalmoscopy," Opt. Express 10,1542-1549 (2002)[REMOVED HYPERLINK FIELD].
[PubMed]

M. Wojtkowski, V. J. Srinivasan, T. H. Ko, J. G. Fujimoto, A. Kowalczyk, and J. S. Duker, "Ultrahigh-resolution, high-speed, Fourier domain optical coherence tomography and methods for dispersion compensation," Opt. Express 12, 2404-2422 (2004).
[CrossRef] [PubMed]

N.A. Nassif, B. Cense, B.H. Park,  et al., "In vivo high-resolution video-rate spectral-domain optical coherence tomography of the human retina and optic nerve," Opt. Express 12, 367-376 (2004).
[CrossRef] [PubMed]

R. Leitgeb, C. K. Hitzenberger, and A. F. Fercher, "Performance of Fourier domain vs. time domain optical coherence tomography," Opt. Express 11, 889-894 (2003). [REMOVED HYPERLINK FIELD]
[CrossRef] [PubMed]

S. H. Yun, G. J. Tearney, J. F. de Boer, N. Iftimia, and B. E. Bouma, "High-speed optical frequency-domain imaging," Opt. Express 11, 2953-2963 (2003).
[CrossRef] [PubMed]

H. Liang, M. G. Cid, R. G. Cucu, G. M. Dobre, A. G. Podoleanu, J. Pedro, and D. Saunders, "En-face optical coherence tomography - a novel application of non-invasive imaging to art conservation," Opt. Express 13,6133-6144 (2005).
[CrossRef] [PubMed]

B.R. White, M.C. Pierce, N. Nassif,  et al., "In vivo dynamic human retinal blood flow imaging using ultra-highspeed spectral domain optical Doppler tomography," Opt. Express 11, 3490-3497 (2004).
[CrossRef]

J. Zhang and Z. Chen, "In vivo blood flow imaging by a swept laser source based Fourier domain optical Doppler tomography," Opt. Express 13,7449-7457 (2005).
[CrossRef] [PubMed]

C. Xu, D. L. Marks, M. N. Do, and S. A. Boppart, "Separation of absorption and scattering profiles in spectroscopic optical coherence tomography using a least-squares algorithm," Opt. Express 12,4790-4803 (2004).
[CrossRef] [PubMed]

B. Hermann, K. Bizheva, A. Unterhuber, B. Povazay, H. Sattmann, L. Schmetterer, A. F. Fercher and W. Drexler, "Precision of extracting absorption profiles from weakly scattering media with spectroscopic time-domain optical coherence tomography," Opt. Express 12, 1677-1688 (2004).
[CrossRef] [PubMed]

D. X. Hammer, R. D. Ferguson, N. V. Iftimia, T. Ustun, G. Wollstein, H. Ishikawa, M. L. Gabriele, W. D. Dilworth, L. Kagemann, and J. S. Schuman, "Advanced scanning methods with tracking optical coherence tomography," Opt. Express 13,7937-7947 (2005).
[CrossRef] [PubMed]

Opt. Lett (1)

D. J. Faber, E.G. mick, M.C.G. Aalders, T.G. van Leeuwen, "Light absorption of (oxy-)hemoglobin assessed by spectroscopic optical coherence tomography," Opt. Lett 28(16), 1436-38 (2003).
[CrossRef] [PubMed]

Opt. Lett. (2)

Optt. Lett. (1)

D. J. Faber, E.G. Mick, M.C.G. Aalders, T.G. van Leeuwen, "Toward assessment of blood oxygen saturation by spectroscopic optical coherence tomography," Optt. Lett. 30(9), 1015-17 (2005).
[CrossRef]

Proc. SPIE (1)

J.M. Schmitt, Z Guan-Xiong, and J. Miller, "Measurement of blood hematocrit by dual-wavelength near-IR photoplethsymography, " Proc. SPIE 1441, 150-161 (1992).
[CrossRef]

Rep. Prog. Phys. (1)

A. F. Fercher, W. Drexler, C. K. Hitzenberger and T. Lasser, "Optical coherence tomography- principles and application," Rep. Prog. Phys. 66. 239-303 (2003).
[CrossRef]

Other (1)

A. Gh. Podoleanu, M. Seeger, G. M. Dobre, D. J. Webb, D. A. Jackson and F. Fitzke, "Transversal and longitudinal images from the retina of the living eye using low coherence reflectometry," J. Biomed. Opt. 3, 12- (1998).
[CrossRef]

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Figures (9)

Fig. 1.
Fig. 1.

General optical layout of the TSLO/SDLCI instrument.

Fig. 2.
Fig. 2.

TLSLO/SDLCI GUI interface

Fig. 3.
Fig. 3.

Schematic of the automated dispersion compensation algorithm.

Fig. 4.
Fig. 4.

The axial PSF (normalized power spectrum of the interference fringes), a) without dispersion compensation and b) with dispersion compensation

Fig. 5.
Fig. 5.

LCI depth reflectivity profile for sheep blood samples with three different hematocrit ratios.

Fig. 6.
Fig. 6.

Variation of the LCI slope with the hematocrit value.

Fig. 7.
Fig. 7.

(a) TSLO retinal image of a volunteer. (b). OCT image along the horizontal dotted line from (a). (c). OCT image along the vertical dotted line from (a).

Fig. 8.
Fig. 8.

(a) LCI slope statistics for 7 volunteers; (b) Histogram showing the correlation of the measured hematocrit with the normal clinical range.

Fig. 9.
Fig. 9.

(a) TSLO retinal image of volunteer no.1. The bright circled spot indicates the position of the LCI measurement. (b) LCI slope statistics, for volunteer no.1, with head immobilization.

Equations (5)

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S LCI ( z ) = k [ I r I s ( λ , z ) ] 1 2 ,
I s ( λ , z ) = I s 0 ( λ ) exp { [ μ a ( λ , z ) + μ s ( λ , z ) ] z } ,
ln [ S LCI ( z ) ] = ln { k [ I r ( λ ) I s 0 ( λ ) ] 1 2 } { [ μ a ( λ , z ) + μ s LCI ( λ , z ) ] z }
s = [ μ a ( λ , z ) + μ s LCI ( λ , z ) ]
l z = 0.44 λ 0 2 n ¯ Δ λ ,

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